The autonomic nervous system is separated into the cholinergic and adrenergic nervous systems. Norepinephrine, the neurotransmitter of the adrenergic nervous system, exerts its activity by interaction with receptors (adrenoceptors) on the effector organs or on the nerve endings. The adrenoceptors are of two primary types: .alpha. and .beta.. Based upon selectivity of the receptors for a series of agonists and antagonists, the a adrenoceptors have been subdivided into .alpha..sub.1 and .alpha..sub.2 subtypes.
A large amount of experimental evidence now supports the view that the .alpha..sub.2 subtype is a heterogeneous adrenoceptor class. (For a general review see Timmermans and Van Zwieten, J. Med. Chem., 25, 1389 (1982)). Experiments using 6-chloro-9-(3-methyl-2-butenyloxy)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzaz epine (SK&F 104078) demonstrated that the classical adrenoceptors are heterogeneous and can be divided into SK&F 104078-insensitive and SK&F 104078-sensitive .alpha..sub.2 adrenoceptors. The latter variously are referred to as postjunctional .alpha..sub.2 adrenoceptors or, preferably, .alpha..sub.3 adrenoceptors, U.S. Pat. No. 4,683,229, Jul. 28, 1987.
As one of the primary regulators of peripheral vascular tone, .alpha. adrenoceptors long have been the targets of efforts to develop agents effective in changing vascular tone for use in treating diseases, such as hypertension, in which alterations in vascular resistance produce therapeutic benefits. Antihypertensive compounds presently in clinical use that function via interaction with a adrenoceptors include methyldopa, clonidine, and prazosin. Efforts to modulate sympathetic tone through interactions with a adrenoceptors have resulted in several compounds that interact somewhat selectively with .alpha..sub.1 or .alpha..sub.2 adrenoreceptors. Selective agonists include phenylephrine and methoxamine which preferentially activate .alpha..sub.1 receptors; and clonidine, .alpha.-methyl-norepinephrine, and tramazoline which preferentially activate .alpha..sub.2 adrenoceptors. Examples of selective .alpha.-adrenoceptor antagonists include prazosin which has high selectivity for .alpha..sub.1 adrenoceptors; and the .alpha..sub.2 -selective blockers yohimbine and rauwolscine.
U.S. Pat. Nos. 3,833,591, 3,904,645, and 3,906,000 disclose substituted compounds of the following base structure: ##STR2##
These compounds are useful as hypoglycemic agents.
PCT Application Number WO 87/00522 describes a series of 4-aminotetrahydrobenz[c,d]indoles and tetrahydroazepino[3,4,5-c,d]indoles having the general formula: ##STR3## in which A-B is --CH.sub.2 --CH(NRR)--CH.sub.2 or --CH.sub.2 --CH.sub.2 --NR--CH.sub.2. These compounds are flopamine agonists useful as hypotensives.
U.S. Pat. No. 4,957,914 and PCT Application No. WO 92/05157 describe certain 1,9alkano-bridged-2,3,4,5-tetrahydro-1H-3-benzazepines useful in the treatment of CNS disorders.
U.S. Pat. Nos. 5,006,521, 4,978,660, 4,963,547, and 4,959,360 disclose substituted 3,4,5,6-tetrahydrothieno- and tetrahydrofuro-[4,3,2-ef][3]benzazepines. These compounds are .alpha.-adrenergic receptor antagonists.